The Pharmacokinetics of Anagrelide in Elderly and Young Patients With Essential Thrombocythaemia (ET)

A Phase II, Open-label, Multicentre, Pharmacokinetic, Pharmacodynamic and Safety Study of Anagrelide Hydrochloride in Young (18-50 Years) and Elderly (≥ 65 Years) Patients With Essential Thrombocythaemia.

Age related differences in response to a drug could arise from variation in pharmacokinetic (PK) and/or pharmacodynamic (PD) profiles between age groups. Whilst the efficacy and safety profile of anagrelide is well established through a well-documented clinical trial programme in patients of all ages, no formal studies have been carried out to investigate whether the PK profile of anagrelide and its metabolites is altered with age.

This study is designed to allow comparisons to be made in terms of pharmacokinetics of anagrelide and its metabolites between elderly (≥ 65 years) and young (18-50 years) ET patients

Study Overview

• Status: Completed
• Conditions: Essential Thrombocythaemia
• Intervention / Treatment: Drug: anagrelide hydrochloride; Drug: anagrelide hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Hospitl Del Mar
• Sweden
  • Lulea, Sweden
    • Quintiles Hermelinen
  • Uppsala, Sweden, 75185
    • Uppsala Akademiska Sjukhus
  • Uppsala, Sweden
    • Quintiles AB Phase I Unit
• United Kingdom
  • Belfast, United Kingdom
    • Belfast City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Young patients aged 18-50 years inclusive or Elderly patients aged 65 years and over
• Patients must have a confirmed diagnosis of ET.
• Currently receiving anagrelide hydrochloride at a stable maintenance dose < 5 mg/day for at least 4 weeks.

Exclusion Criteria:

• Diagnosis of any other myeloproliferative disorder.
• Current use of tobacco in any form (e.g. smoking or chewing)
• Treatment with any known enzyme altering agents (barbiturates, phenothiazines, cimetidine etc.) within 30 days prior to or during the study.
• Patients for whom use of another cytoreductive agent in addition to anagrelide is considered necessary for control of platelet count.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Younger Participants (18-50 years)	Drug: anagrelide hydrochloride; Anagrelide hydrochloride 0.5 mg per capsule; participants will be stable on an anagrelide treatment regimen and will take capsules from their own prescription except on the PK day when the participant specific anagrelide dose will be administered from a controlled study specific supply.; Drug: anagrelide hydrochloride; Anagrelide hydrochloride 0.5 mg per capsule; participants will be stable on an anagrelide regimen and will take capsules from their own prescription except on the PK day when the participant specific anagrelide dose will be administered from a controlled study specific supply.
EXPERIMENTAL: Elderly Participants (≥65 years)	Drug: anagrelide hydrochloride; Anagrelide hydrochloride 0.5 mg per capsule; participants will be stable on an anagrelide treatment regimen and will take capsules from their own prescription except on the PK day when the participant specific anagrelide dose will be administered from a controlled study specific supply.; Drug: anagrelide hydrochloride; Anagrelide hydrochloride 0.5 mg per capsule; participants will be stable on an anagrelide regimen and will take capsules from their own prescription except on the PK day when the participant specific anagrelide dose will be administered from a controlled study specific supply.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of Agrylin		over 1 day
Time of Maximum Plasma Concentration (Tmax) of Agrylin		over 1 day
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Agrylin		over 1 day
Terminal Half-life (T 1/2) of Agrylin		over 1 day
Total Clearance (CL/F) of Agrylin		over 1 day
Volume of Distribution (Vz/F) of Agrylin		over 1 day
Cmax of Active Metabolite	An active metabolite has therapeutic activity similar to the parent compound and must be considered in therapeutic pharmacokinetics.	over 1 day
Tmax of Active Metabolite		over 1 day
AUC of Active Metabolite		over 1 day
T 1/2 of Active Metabolite		over 1 day
CL/F of Active Metabolite		over 1 day
Vz/F of Active Metabolite		over 1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet Count	Platelet counts in patients with ET receiving Agrylin	over 1 day
Heart Rate	Heart rates in patients with ET receiving Agrylin	over 1 day
Systolic Blood Pressure	Systolic blood pressures in patients with ET receiving Agrylin	over 1 day
Diastolic Blood Pressure	Diastolic blood pressures in patients with ET receiving Agrylin	over 1 day

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Besses C, Zeller W, Alvarez-Larran A, Coll R, Troy S, Purkayastha J, Martin P, Freitag C. Pharmacokinetics and tolerability of anagrelide hydrochloride in young (18 - 50 years) and elderly (>/= 65 years) patients with essential thrombocythemia. Int J Clin Pharmacol Ther. 2012 Nov;50(11):787-96. doi: 10.5414/CP201711.

Helpful Links

• FDA Recall Information
• FDA-approved Label

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 13, 2006
• Primary Completion (ACTUAL): January 22, 2008
• Study Completion (ACTUAL): January 22, 2008

Study Registration Dates

• First Submitted: December 19, 2006
• First Submitted That Met QC Criteria: December 19, 2006
• First Posted (ESTIMATE): December 20, 2006

Study Record Updates

• Last Update Posted (ACTUAL): June 29, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Thrombocytosis; Thrombocythemia, Essential; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Anagrelide
• Other Study ID Numbers: SPD422-203; 2004-004058-20 (EUDRACT_NUMBER)